Cancer is defined that “normal cells which can be regularly proliferated and suppressed in an object if necessary and non-differentiated cells which are unlimitedly proliferated regardless of a required state in a tissue unlike the normal cells are constituted to form a tumor”, and the normal cells in the body are changed in genes in the cells due to a specific reason to be modified into cancer cells. All over the world, the cancer occupies approximately 13% of the entire death causes, and is caused without distinction of sex and age and a terrible disease which occupies a second death cause in the worldwide and a first death cause in Korea, and thus researches for targeting conquer cancer have been actively conducted. In the researches, development of efficient anticancer agents which have fewer side effects and can overcome resistance due to diversity of the cancer and diversification of pathogenesis has been required and new anticancer agents are being continuously released.
A stimulus-response system means that a carrier causes changes in phase transition, swelling, degradation, and the like in response to an external environment such as a pH, a temperature, an ionic strength, an electric field, a magnetic field, light, and an ultrasonic wave. The stimulus-response system is mainly used in a release control system induced to protect a drug and adjust a release speed of the drug, or leave the drug in a specific portion. Particularly, the pH of the cancer portion is different from a pH (7.4±0.04) in a general body and various functional groups sensitive to the pH are present and thus, the stimulus-response system has been very widely used.
Meanwhile, cinnamaldehyde is a main component of cinnamon bark as a main active ingredient of cinnamomum cassia in the Lauraceae plant which has been used for treating dyspepsia, gastritis, blood circulation disorders, and inflammation in both East and West. The cinnamaldehyde is a material which includes a α,β-carbonyl group which is known as a Michael receptor pharmacophore, generates reactive oxygen species (ROS) to deteriorate a mitochondrial membrane potential, and thus releases a cytochrome C to a cytosol in the cells to induce apoptosis, and anticancer ability through a mechanism depending on caspase has been proved. However, in spite of excellent anticancer abilities of the cinnamaldehyde and derivatives thereof, phagocytosis is rapidly performed by liver macrophagocytic cells in the body and there is a disadvantage that there is no ability capable of targeting the cancer due to a short half-life of less than 1.5 hr (several minutes and approximately 5 min). Therefore, in order to apply the cinnamaldehyde to an anticancer treatment in clinical, development of physical and chemical modification or new drug delivery systems for enhancing the anticancer effect has been required.
Further, it is known that quinone methide reacts with glutathione (GSH) as a required antioxidant enzyme in the cancer cells to decrease an antioxidative level and thus relatively increases oxidation stress and causes an anticancer effect.
Therefore, the present inventors conducted researches for preparing a hybrid anticancer prodrug which enhances a short retention time which is a disadvantage of cinnamaldehyde inducing apoptosis and a medicinal effect and performs synergetic action to enhance the effect thereof. As a result, the present inventors synthesized 4-(1,3,2-dioxaborinan-2-yl)benzyl ((5-methyl-2-styryl-1,3-dioxan-5-yl)methyl)carbonate (QCA) and 4-(1,3,2-dioxaborinan-2-yl)benzyl ((5-methyl-2-(2-benzoyloxyphenyl)vinyl-1,3-dioxan-5-yl)methyl)carbonate (QBCA) which are prodrugs simultaneously generating cinnamaldehyde and quinone methide, verified a possibility as a new anticancer therapeutic agent of the prepared QCA and QBCA which enhances the retention time of the cinnamaldehyde, minimize side effects by selectively acting in the cancer cells, and maximally have the anticancer effect to complete the present invention.